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Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release

Summary: Synaptotagmin-IV modulates synaptic function and
long-term potentiation by regulating BDNF release
Camin Dean1,2, Huisheng Liu1,2, F Mark Dunning1,2, Payne Y Chang1, Meyer B Jackson1 &
Edwin R Chapman1,2
Synaptotagmin-IV (syt-IV) is a membrane trafficking protein that influences learning and memory, but its localization and role in
synaptic function remain unclear. We found that syt-IV localized to brain-derived neurotrophic factor (BDNF)-containing vesicles
in hippocampal neurons. Syt-IV/BDNF­harboring vesicles underwent exocytosis in both axons and dendrites, and syt-IV inhibited
BDNF release at both sites. Knockout of syt-IV increased, and overexpression decreased, the rate of synaptic vesicle exocytosis
from presynaptic terminals indirectly via changes in postsynaptic release of BDNF. Thus, postsynaptic syt-IV regulates the
trans-synaptic action of BDNF to control presynaptic vesicle dynamics. Furthermore, selective loss of presynaptic syt-IV increased
spontaneous quantal release, whereas a loss of postsynaptic syt-IV increased quantal amplitude. Finally, syt-IV knockout mice
showed enhanced long-term potentiation (LTP), which depended entirely on disinhibition of BDNF release. Thus, regulation of
BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP.
Synaptic plasticity relies on highly regulated membrane fusion events
on both sides of the synapse, including presynaptic neurotransmitter
release, neuropeptide release and postsynaptic receptor trafficking.
Regulation of these fusion events allows synapses to adjust their
strength in response to stimulation. Many of the 17 members of the
synaptotagmin family of proteins promote membrane fusion by
penetrating lipid bilayers and binding to soluble NSF attachment


Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago
Kalil, Ronald E. - Neuroscience Training Program & W.M. Keck Laboratory for Biological Imaging, University of Wisconsin at Madison


Collections: Biology and Medicine